AI Article Synopsis
- - The human constitutive androstane receptor (hCAR) is important for regulating how the body breaks down foreign substances, but a method for studying its binding with various compounds was needed.
- - Researchers identified the compound SNS-032 and its derivative THAL-SNS-032 as candidates that bind to hCAR, leading to the development of a fluorescent probe called BODIPY FL SNS-032 that can effectively measure these interactions.
- - BODIPY FL SNS-032 not only binds strongly to hCAR (with a binding affinity of around 300 nM) but also has significant binding affinities to various kinases, making it a useful tool for studying both hCAR and kinase function.
Article Abstract
Human constitutive androstane receptor (hCAR) regulates xenobiotic metabolism. Its large and flexible ligand binding pocket can accommodate structurally diverse compounds. An assay for characterizing the binding of ligands to hCAR is needed but has not been reported. Here, we first discovered the promiscuous kinase inhibitor SNS-032 and its derivative THAL-SNS-032 as binders of hCAR, then developed BODIPY FL SNS 032 () as a high-affinity hCAR fluorescent probe ( : 300 ± 30 nM) in a TR-FRET binding assay and used it to characterize hCAR ligands for their competitive binding activities. BODIPY FL SNS 032 also displayed high binding affinities to multiple kinases, such as hGSK3A ( : 4.5 ± 0.2 nM), hCDK9/CycT1 ( : 5.1 ± 0.6 nM), hMAPK15 ( : 340 ± 20 nM), hCASK ( : 550 ± 30 nM), and hCAMKK2 ( : 530 ± 40 nM). BODIPY FL SNS 032 is therefore a versatile probe for hCAR and multiple kinases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571093 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.4c00416 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!